Reproductive efficiency, which can be defined as the number of pigs produced per breeding female, is the major limiting factor in the efficient production of pork. The number of pigs born alive in the United States averages approximately 9.5 pigs per litter. Heritability for litter size is low (10%-15%), and standard genetic methods of selecting breeding females on the basis of past litter size have not been effective. Therefore, there is a need for an approach that deals with selection for reproduction at the cellular or DNA level.
Chinese breeds are known for reaching puberty at an early age and for their large litter size. American breeds are known for their greater growth rates and leanness. Thus, it would be desirable to combine the best characteristics of both types of breeds, thereby improving the efficiency of U.S. pork production. These efforts would be greatly assisted by the discovery of genes or genetic markers that are associated with increased litter size in pigs.
RFLP analysis has been used by several groups to study pig DNA. Jung et al., Theor. Appl. Genet., 77:271-274 (1989), incorporated herein by reference, discloses the use of RFLP techniques to show genetic variability between two pig breeds. Polymorphism was demonstrated for swine leukocyte antigen (SLA) Class I genes in these breeds. Hoganson et al., Abstract for Annual Meeting of Midwestern Section of the American Society of Animal Science, Mar. 26-28, 1990, incorporated herein by reference, reports on the polymorphism of swine major histocompatibility complex (MHC) genes for Chinese pigs, also demonstrated by RFLP analysis. Jung et al. Animal Genetics, 26:79-91 (1989), incorporated herein by reference, reports on RFLP analysis of SLA Class I genes in certain boars. The authors state that the results suggest that there may be an association between swine SLA/MHC Class I genes and production and performance traits. They further state that the use of SLA Class I restriction fragments, as genetic markers, may have potential in the future for improving pig growth performance.
Further, U.S. Pat. No. 5,550,024 to Rothschild et. discloses a polymorphism in the pig estrogen receptor gene which is associated with larger litter size, the disclosure of which is incorporated herein by reference.
Another pig hormone related to reproductive success is Prolactin. Prolactin (PRL) is an anterior pituitary peptide hormone involved in many different endocrine activities, but is essential for reproductive success. One of its best characterized functions is regulating milk production in adult mammals. PRL is required for the stimulation of lactogenesis, or synthesis of milk proteins. This action is mediated by its receptor (PRLR). PRLR belongs to the cytokine/GHR/PRLR superfamily. When activated by PRL, PRLR begins a signal transduction pathway, which ultimately activates transcription of genes such as .beta.-casein and .alpha.-lactalbumin. When activated by PRL, PRLR begins a signal transduction pathway thought to involve the tyrosine kinase Jak2. Mutations in the carboxy-terminal end of the protein which change a specific phosphotyrosine residue prevents the receptor from activating Jak2 and ultimately interferes with the activation of transcription of the .beta.-casein gene (Lebrun). Long and short forms of the receptor protein, as well as various transcript sizes have been characterized in the rat, mouse, rabbit, and human. (Boutin, Edery, Lesueur). However, it has been demonstrated that the short form is not capable of activating transcription of the milk protein genes. The mRNAs seen thus far originate from the same primary transcript and are due to alternative splicing, specifically in the untranslated regions in the rabbit and human. Recently, PRL has also been shown to stimulate the production of progesterone, required for maintenance of pregnancy, in large porcine luteal cells in vitro. PRLR is thought to mediate the effects of growth hormone (bST) injections on higher milk yield in cattle, and thus may be important in varying milk yield in pigs. In humans and mice, the growth hormone receptor (GHR) and PRLR map close together (Arden et al., 1990; Barker et al., 1992), making it likely that these two genes are linked in pigs. GHR has been mapped in pigs to chromosome 16, while PRLR is unmapped and no genetic variability has been reported for PRLR.
The present invention provides a genetic marker, based upon the discovery of polymorphisms in the prolactin receptor gene, which relates to increased average litter size in pigs. This will permit genetic typing of pigs for their prolactin receptor genes and for determination of the relationship of specific RFLPs to increased litter size. It will also permit the identification of individual males and females that carry the gene for larger litters. In the case of females it would permit that a female would be expected to produce a litter size larger than the average for their breed, or in the case of males for their female offspring to have larger litters than the breed average. Thus, the markers will be selection tools in breeding programs to develop lines and breeds that produce litters containing a larger number of offspring.